Nucleotide-binding oligomerization domain-like receptors (“NLRs”) include a family of intracellular receptors that detects pathogen-associated molecular patterns (“PAMPs”) and endogenous molecules (see, e.g., P.-Y. Ting, et al., “The NLR gene family: a standard nomenclature,” Immunity, vol. 28, no. 3, pp. 285-287, 2008).
NLRPs represent a subfamily of NLRs that include a Pyrin domain and are constituted by proteins such as NLRP1, NLRP3, NLRP4, NLRP6, NLRP7, and NLRP12. NLRPs are believed to be involved with the formation of multiprotein complexes termed inflammasomes (see, e.g., C. Chaput, et al., “NOD-like receptors in lung diseases,” Frontiers in Immunology, vol. 4, article 393, 2013). These complexes typically include one or two NLR proteins, the adapter molecule apoptosis associated speck-like containing a CARD domain (ASC) and pro-caspase-1 F (see, e.g., Bauernfeind and V. Hornung, “Of inflammasomes and pathogens—sensing of microbes by the inflammasome,” EMBO Molecular Medicine, vol. 5, no. 6, pp. 814-826, 2013).
One such inflammasome is formed by the NLRP3 scaffold, the ASC adaptor and caspase-1 (see, e.g., J. A. Hirota, et al., “The airway epithelium nucleotide-binding domain and leucine-rich repeat protein 3 inflammasome is activated by urban particulate matter,” Journal of Allergy and Clinical Immunology, vol. 129, no. 4, pp. 1116.e6-1125.e6, 2012), and its expression is believed to be induced by inflammatory cytokines and TLR agonists in myeloid cells and human bronchial epithelial cells (Id). The NLRP3 inflammasome is believed to mediate the caspase-1-dependent conversion of pro-IL-1β and pro-IL-18 to IL-1β and IL-18. Further, IL-1β and IL-18 have been shown to play an important role in the treatment of various types of cancer (see, e.g., EMBO Mol Med. 2012 4:1276 and PLoS One 2011 6:e24241). IL-18 has been shown to override resistance to checkpoint inhibitors in colon cancer tumor models (see Clin. Cancer Res. 2016 Jan. 11. pii: clincanres.1655.2015).